Electroporation for obesity or diabetes treatment

ABSTRACT

Endolumenal devices and methods can be used for the treatment of health conditions including obesity and diabetes. In some embodiments, the methods and systems provided herein can cause weight loss or control diabetes by reducing the caloric absorption of an individual. For example, this document provides several devices and methods for treating obesity and diabetes by using electroporation to modulate the duodenal mucosa. In addition, this document provides devices and methods for bypassing portions of the gastrointestinal tract to reduce nutritional uptake.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Application Ser. No.62/238,191, filed on Oct. 7, 2015. This disclosure of the priorapplication is considered part of (and is incorporated by reference in)the disclosure of this application.

BACKGROUND 1. Technical Field

This document relates to devices and methods for the treatment of healthconditions including obesity and diabetes. For example, this documentrelates to devices and methods for treating obesity and diabetes usingelectroporation endoscopically.

2. Background Information

Obesity is a global problem crossing age, ethnic, and socioeconomicboundaries. In general, obesity means having too much body fat. Morbidobesity is a serious health condition that can interfere with basicphysical functions such as breathing or walking. Individuals who aremorbidly obese are at greater risk for illnesses including diabetes,high blood pressure, sleep apnea, gastroesophageal reflux disease,infertility, low back pain, asthma, gallstones, osteoarthritis, heartdisease, and cancer. Billions of dollars are spent each year treatingmillions of individuals around the world suffering from such diseases.Many people suffering from morbid obesity find it nearly impossible tolose weight by controlling their diet and exercising.

Type 2 diabetes is a chronic condition that affects the way a bodymetabolizes sugar (glucose). With type 2 diabetes, the body eitherresists the effects of insulin a hormone that regulates the movement ofsugar into cells—or doesn't produce enough insulin to maintain a normalglucose level. More common in adults, type 2 diabetes increasinglyaffects children as childhood obesity increases. There is no known curefor type 2 diabetes. In some cases it may be managed by eating well,exercising and maintaining a healthy weight. If diet and exercise aren'tenough to manage blood sugar well, diabetes medications or insulintherapy may be needed.

Ablation/electroporation therapy is a type of minimally invasiveprocedure used to destroy tissue associated with various conditions. Forexample, ablation procedures can be used to treat tumors or to destroyheart tissue that's causing abnormally rapid heart rhythms. Ablationtherapy may be administered using probes inserted through the skin,flexible tubes (catheters) inserted through a body conduit, or energybeams to reach the area being treated. Imaging techniques may be used toguide the ablation. The tissue is injured or destroyed with heat (e.g.,radiofrequency ablation), extreme cold (cryoablation), lasers or achemical.

SUMMARY

This document provides devices and methods for the treatment of healthconditions including obesity and diabetes. In some embodiments, themethods and systems provided herein can cause weight loss or controldiabetes by reducing the caloric absorption of an individual, byincreasing levels of gut hormones important in appetite regulation andinsulin secretion, and/or by reshaping the mucosa of the smallintestines. For example, this document provides several devices andmethods for treating obesity and diabetes by using electroporation tomodulate the duodenal mucosa. In addition, this document providesdevices and methods for bypassing portions of the gastrointestinal (GT)tract to reduce nutritional uptake.

In one implementation, an electroporation device includes a shaftdefining a first lumen therethrough; a proximal ballooncircumferentially attached about a distal portion of the shaft; a middleportion extending distally of the proximal balloon; and a distal balloonextending distally of the middle portion. The middle portion defines amiddle portion lumen in communication with the first lumen. The middleportion includes one or more electrodes configured to administerelectroporation energy. The middle portion includes one or moreapertures through a wall of the middle portion and in communication withthe middle portion lumen. The middle portion has a longitudinallycontracted configuration and a longitudinally extended configurationthat is longer than the longitudinally contracted configuration. In someembodiments, the middle portion has a fixed length.

Such an electroporation device may optionally include one or more of thefollowing features. The distal balloon may have a distal balloon lumentherethrough that is in communication with the middle portion lumen. Thedistal balloon lumen may be defined by a distal shaft on which thedistal balloon is circumferentially attached. The shaft may define aproximal balloon inflation lumen in communication with the proximalballoon. The shaft and the middle portion may define a distal ballooninflation lumen in communication with the distal balloon. The middleportion may comprise an accordion configuration that facilitates themiddle portion to reconfigure between the longitudinally contractedconfiguration and the longitudinally extended configuration. The firstlumen and the middle portion lumen may be configured to receive anendoscope or to advance through the working channel of an endoscope.This catheter can also be advanced over a guide wire under endoscopicand/or fluoroscopic guidance.

In another implementation, a method of administering electroporationenergy to patient includes deploying an electroporation device at atarget location within the patient, energizing the one or moreelectrodes with electroporation energy, and, while energizing the one ormore electrodes, supplying electrically conductive liquid into theelectroporation device such that the electrically conductive liquidflows through the one or more apertures. The electroporation deviceincludes a shaft defining a first lumen therethrough; a proximal ballooncircumferentially attached about a distal portion of the shaft; a middleportion extending distally of the proximal balloon; and a distal balloonextending distally of the middle portion. The middle portion defines amiddle portion lumen in communication with the first lumen. The middleportion includes one or more electrodes configured to administerelectroporation energy. The middle portion includes one or moreapertures through a wall of the middle portion and in communication withthe middle portion lumen. The middle portion has a longitudinallycontracted configuration and a longitudinally extended configurationthat is longer than the longitudinally contracted configuration. In someembodiments, the middle portion has a fixed length.

Such a method of administering electroporation energy to patient mayoptionally include one or more of the following features. The targetlocation may be a duodenum or a jejunum. The method may furthercomprise, before supplying electrically conductive liquid into theelectroporation device, inflating the proximal balloon and the distalballoon. The method may further comprise, before supplying electricallyconductive liquid into the electroporation device, extending the middleportion to reconfigure the middle portion from the longitudinallycontracted configuration to the longitudinally extended configuration.The electrically conductive liquid may carry the electroporation energyfrom the one or more electrodes to tissue of the patient. The method mayfurther comprise installing an endoscope shaft into the first lumen andthe middle portion lumen, and using a single or double channel endoscopeto deploy the electroporation device and or inject the electricallyconductive liquid. This catheter can also be advanced over a guide wireunder endoscopic and/or fluoroscopic guidance.

In another implementation, an electroporation device includes a shaftdefining a lumen therethrough; a balloon circumferentially attachedabout a distal portion of the shaft, wherein the balloon has alongitudinal length between 5 to 20 cm; and one or more electrodesdisposed on an outer surface of the balloon. The lumen is configured toreceive an endoscope therein. In some embodiments, the balloon is aporous material that facilitates passage of an electrically conductiveliquid therethrough. This catheter can also be advanced over a guidewire under endoscopic and/or fluoroscopic guidance.

In another implementation, a method of treating a patient includesdeploying an electroporation device at a target location within anintestine of the patient. The electroporation device includes a shaftdefining a first lumen therethrough; a distal balloon circumferentiallyattached about a distal portion of the shaft; a middle portion extendingproximal to the distal balloon, where the electroporation electrodes aremounted; and an overtube with proximal balloon delivered over a singleor double channel endoscope capable of inflating and deflating separatefrom distal balloon. The electroporation catheter is advanced throughthe working channel of the single or double channel endoscope to delivertherapy to the target tissue. The inflated distal balloon on theelectroporation catheter and the inflated proximal balloon on theovertube over the endoscope provide a seal to create a column ofelectrically conductive liquid injected through the working channel ofthe endoscope.

In another implementation, a method of treating a patient includesdeploying an electroporation device at a target location within anintestine of the patient. The electroporation device/catheter includes ashaft defining a first lumen therethrough, with no balloon on this shaftjust electrodes delivered through the working channel of a single ofdouble channel endoscope. An overtube with two balloons (proximal anddistal) separated by a tissue supporting structure to spread theduodenal or jejunal folds is delivered over a single or double channelendoscope to the target small intestinal segment. The endoscope isretracted from the distal overtube balloon and a self sealing valve inthe lumen of the distal portion of the overtube/distal balloon issealed. After the proximal balloon is inflated and electricallyconductive liquid is injected through the working channel of theendoscope to create a liquid column. The electroporation catheter isthen delivered through the endoscope into the liquid column to deliverthe electroporation current. In one example, the tissue supportingstructure can be a collapsible/expandable stent or mesh, while in itsexpanded configuration the tissue supporting structure can spread mucosafolds to increase the surface area of mucosa that is accessible andexposed to the conductive liquid.

In another implementation, a method of treating a patient includesdeploying an electroporation device at a target location within anintestine of the patient. The electroporation device includes a shaftdefining a first lumen therethrough; a proximal ballooncircumferentially attached about a distal portion of the shaft; a middleportion extending distally of the proximal balloon; and a distal balloonextending distally of the middle portion. The middle portion defines amiddle portion lumen in communication with the first lumen. The middleportion includes one or more electrodes configured to administerelectroporation energy. The middle portion includes one or moreapertures through a wall of the middle portion and in communication withthe middle portion lumen. The middle portion has a longitudinallycontracted configuration and a longitudinally extended configurationthat is longer than the longitudinally contracted configuration.

Such a method of treating a patient may optionally include one or moreof the following features. The method may further comprise energizingthe one or more electrodes with electroporation energy. The method mayfurther comprise supplying liquid into the electroporation device suchthat the liquid flows through the one or more apertures and into theintestine. The liquid may comprise medicinal solutions or drugs. Themethod may further comprise stretching at least a portion of theintestine to increase an intestinal surface area in contact with theliquid.

Such a method of treating a patient may optionally include one or moreof the following features. The liquid may comprise medicinal solutionsor drugs that can be delivered to target small intestinal cell throughthe process of reversible electroporation. The method may furthercomprise stretching at least a portion of the intestine to increase anintestinal surface area in contact with the liquid. The method mayfurther comprise an over the scope overtube with tissue retractionstructure in between two balloons delivered over an endoscope to createa liquid column with stretch intestinal surface to effectively deliverelectroporation current through a catheter delivered through the workingchannel of the endoscope. Finally, any of the electroporation cathetersdescribed can also be delivered over a guidewire under fluoroscopicguidance.

Particular embodiments of the subject matter described in this documentcan be implemented to realize one or more of the following advantages.In some embodiments, methods and systems provided herein provide aminimally invasive weight loss and/or diabetes therapy. For example, insome embodiments electroporation of the duodenal mucosa is performedendoscopically. Such minimally invasive techniques can reduce recoverytimes, patient discomfort, and treatment costs. In some embodiments, themethods and systems provided herein alter the body's ability to processsugar and may improve glycemic control for patients with Type 2diabetes. Additionally, these catheters and/or overtubes can be used toablate other portions of the gastrointestinal tract where superficialmucosal ablation can be utilized such as in the treatment of metaplasia,dysplasia, or superficial neoplasia of the gastrointestinal tract and/orcystic neoplasms of the pancreas where the electroporation catheter withelectrodes is delivered through a 19 gauge endoscopic ultrasound needleto the cyst under endosonographic guidance.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used to practicethe invention, suitable methods and materials are described herein. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description herein. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of a portion of a human GI tract,including a stomach and duodenum.

FIG. 2 is a plan view of a device for administering electroporation to aGI tract (e.g., duodenum) in accordance with some embodiments providedherein. The device is shown in an expanded configuration.

FIG. 3 is a plan view of the device of FIG. 2 shown in a contracteddelivery configuration.

FIG. 4 shows the device of FIGS. 2 and 3 deployed in a duodenum in anarrangement where the device can provide an electroporation treatment tomodulate the duodenal mucosa.

FIG. 5 is a plan view of another device for administeringelectroporation to a GI tract (e.g., duodenum) in accordance with someembodiments provided herein. The device is shown in an expandedconfiguration.

FIG. 6 is a plan view in longitudinal cross-section of another devicefor administering electroporation to a GI tract (e.g., duodenum) inaccordance with some embodiments provided herein. The device is shown inan expanded configuration.

FIG. 7 shows the device of FIG. 5 or 6 deployed in a duodenum in anarrangement where the device can provide an electroporation treatment tomodulate the duodenal mucosa.

FIG. 8 is a plan view of another device for administeringelectroporation to a GI tract in accordance with some embodimentsutilizing a proximal balloon mounted on an overtube on the endoscope.The electroporation catheter with its distal balloon is deliveredthrough the working channel of the endoscope to deliver electroporation.

FIG. 9 shows the device of FIG. 8 deployed in a duodenum in anarrangement where the device can provide an electroporation treatment tomodulate the duodenal mucosa.

FIG. 10 is a plan view of another device for administeringelectroporation to a GI tract in accordance with some embodiments.

FIG. 11 shows the device of FIG. 10 deployed in a duodenum in anarrangement where the device can provide an electroporation treatment tomodulate the duodenal mucosa.

FIG. 12 is a plan view of another device for administeringelectroporation to a GI tract in accordance with some embodiments.

FIG. 13 shows the device of FIG. 12 deployed in a duodenum in anarrangement where the device can provide an electroporation treatment tomodulate the duodenal mucosa.

Like reference numbers represent corresponding parts throughout.

DETAILED DESCRIPTION

This document provides devices and methods for the treatment of healthconditions including obesity and diabetes. In some embodiments, themethods and systems provided herein can cause weight loss and/or cancontrol diabetes by reducing the caloric absorption of an individual, byincreasing levels of gut hormones important in appetite regulation andinsulin secretion, and/or by reshaping the mucosa of the smallintestines. For example, this document provides several devices andmethods for treating obesity and diabetes by using electroporation tomodulate the duodenal mucosa. In addition, this document providesdevices and methods for bypassing portions of the GI tract to reducenutritional uptake.

Referring to FIG. 1, a human GI tract portion 100 includes a stomach 110and a duodenum 120. The lining of duodenum 120 is made up of duodenalmucosa 122. Duodenal mucosa 122 is made up of short tubularinvaginations called crypts, where intestinal stem-cells (cells that candifferentiate to a different cell type) and paneth cells (cells thatfuel the activity of stem cells) reside. Duodenal mucosa 122 alsoincludes villi, where enterocytes (columnar epithelium consisting of onelayer of tall rectangular cells concerned with absorbing nutrients fromthe gut); goblet cell (cells that produce alkaline mucus to protect thesmall intestines); and enteroendocrine cells (specialized endocrinecells of the gastrointestinal tract that produce gastrointestinalhormones important for digestion and glucose control) reside.

As described further below, devices and methods for administeringelectroporation to modulate the duodenal mucosa 122 are provided herein.Moreover, using the provided devices and methods for administeringelectroporation, the depths and cell composition of the crypts and villiof duodenal mucosa 122 can be modulated. Using such devices andtechniques, weight loss and/or control of diabetes by reducing thecaloric absorption, by increasing gut hormones, and/or by re-setting thediseased intestinal mucosa of an individual can be achieved.

Referring to FIG. 2, an example mucosa electroporation device 200includes a proximal shaft 210 a, a proximal balloon 220, a distalballoon 230, a distal shaft 210 b, and a middle portion 240. Proximalballoon 220 is attached to proximal shaft 210 a in a circumferentialfashion. Middle portion 240 is attached to proximal shaft 210 a andextends distally from proximal shaft 210 a. The distal end of middleportion 240 is attached to distal shaft 210 b. Distal balloon 230 isattached to distal shaft 210 b in a circumferential fashion.

Proximal shaft 210 a, middle portion 240, and distal shaft 210 b definea lumen 212. In some embodiments, lumen 212 is sized to slidably receivean endoscope shaft. In some embodiments, lumen 212 is sized to slidablyreceive a guidewire.

Proximal balloon 220 and distal balloon 230 are inflatable members.Accordingly, inflation media (e.g., saline, water, CO2, air, etc.) canbe supplied to proximal balloon 220 and distal balloon 230 to causetheir inflation. In some embodiments, the wall of proximal shaft 210 adefines an inflation lumen through which inflation media is supplied toproximal balloon 220. In some embodiments, (i) the wall of proximalshaft 210 a, (ii) the wall of middle portion 240, and (iii) the wall ofdistal shaft 210 b defines an inflation lumen through which inflationmedia is supplied to distal balloon 230. Accordingly, in someembodiments the inflation and deflation of proximal balloon 220 anddistal balloon 230 can be controlled separately. Alternatively, in someembodiments the inflation and deflation of proximal balloon 220 anddistal balloon 230 are controlled unitarily. While balloons 220 and 230are deflated, in some embodiments mucosa electroporation device 200 canpass through the working channel of an endoscope.

Proximal balloon 220 and distal balloon 230 are flexible, elastic,conformable balloon members. In some embodiments, proximal balloon 220and distal balloon 230 are made from silicone, or latex, or other typescompliable materials. Accordingly, when inflated, proximal balloon 220and distal balloon 230 are conformable to the topography of the GIconduit. Therefore, proximal balloon 220 and distal balloon 230, wheninflated, provide a substantial seal against the wall of the GI conduit.While in some embodiments proximal balloon 220 and distal balloon 230are made from the same material, in some embodiments proximal balloon220 and distal balloon 230 are made from dissimilar materials.

In some embodiments, the maximum outer diameter of proximal balloon 220and/or distal balloon 230, when inflated, is in a range from about 30 mmto about 50 mm. The maximum inflated outer diameter of proximal balloon220 and distal balloon 230 is scalable to any suitable size. Forexample, in some embodiments the maximum outer diameter of proximalballoon 220 and/or distal balloon 230, when inflated, is in a range fromabout 35 mm to about 45 mm, or from about 40 mm to about 50 mm, or fromabout 30 mm to about 40 mm, or from about 25 mm to about 35 mm, or fromabout 30 mm to about 60 mm. In some embodiments, the maximum outerdiameters of proximal balloon 220 and distal balloon 230 are equal toeach other. In some embodiments, the maximum outer diameters of proximalballoon 220 and distal balloon 230 are unequal.

As described further below, distal shaft 210 b or distal balloon 230includes a valve 232 disposed within the lumen 212. Valve 232 allowspassage of an instrument (e.g., an endoscope or guidewire) therethrough.But, when no such instrument is in contact with valve 232, valve 232acts as a closure at the distal end of lumen 212 so that lumen 212 isdead ended at or near distal balloon 230.

Middle portion 240 is longitudinally extendable and laterallydeflectable and flexible. In the depicted embodiment, middle portion 240is configured as an accordion member having multiple pleats and multipleflexible, extendable portions 242. In some embodiments, middle portion240 is configured in other arrangements that are longitudinallyextendable and laterally flexible. For example, and without limitation,in some embodiments middle portion 240 is configured as a coil (e.g.,helically), an elastic member, an inter-foldable member, a rolled-upmember, a telescoping member, and the like, and combinations thereof.

In some embodiments, middle portion 240, when fully longitudinallyextended, is about 30 cm in length. The fully longitudinally extendedlength of middle portion 240 is scalable to any suitable size. Forexample, in some embodiments the fully longitudinally extended length ofmiddle portion 240 is in a range from about 25 cm to about 35 cm, orfrom about 30 cm to about 40 cm, or from about 20 cm to about 30 cm, orfrom about 15 cm to about 35 cm, or from about 25 cm to about 50 cm.

Middle portion 240 is configured to facilitate electroporation.Accordingly, middle portion 240 includes one or more electrodes 244.Electrodes 244 can be different types of electrodes, and/or electrodes244 can be configured to deliver different types of energy in differentembodiments of electroporation device 200. For example, in the depictedembodiment electrodes 244 are DC electrodes. Alternatively, oradditionally, mucosa electroporation device 200 can be configured todeliver other types of electroporation energy such as, but not limitedto, radiofrequency (RF), AC, cryogenic, chemical, and the like. In someembodiments, a combination of such energy sources can be used within asingle embodiment of electroporation device 200 (e.g., RF and DC areused in combination is some embodiments). The electroporation energy canbe monopolar or bipolar. Electrodes 244 can be electrically wired to anelectroporation energy source (not shown) located external to thepatient. In some implementations, two or more types of electroporationenergy sources can be coupled to electrodes 244. For example, in oneparticular non-limiting implementation a RF source and a NANOKNIFE®irreversible electroporation system by AngioDynamics, Inc. are bothcoupled to electrodes 244 such that a switch box is used to selectbetween the two sources of energy.

Middle portion 240 also includes one or more apertures 246. Apertures246 are openings through the wall of middle portion 240 such that lumen212 is in fluid communication with the exterior of electroporationdevice 200 via apertures 246. In some embodiments, alternatively oradditionally, the material comprising middle portion 240 is porous suchthat lumen 212 is in fluid communication with the exterior of mucosaelectroporation device 200 via the pores of the material. As describedfurther below, apertures 246 can provide passageways for a conductiveliquid that will carry electroporation energy from electrodes 244 to thewall of the tissue structure (e.g., the duodenum) in whichelectroporation device 200 is resident.

Referring also to FIG. 3, in some embodiments electroporation device 200can be configured in a contracted configuration for minimally invasivedeployment into the GI tract. For example, in the depicted arrangementelectroporation device 200 is disposed over an endoscope 300 (only thedistal end portion of endoscope 300 is illustrated), and electroporationdevice 200 is in a radially and longitudinally contracted configuration(as compared to the radially expanded and longitudinally extendedconfiguration of FIG. 2). Endoscope 300 is disposed within lumen 212.Proximal balloon 220 and distal balloon 230 are deflated such that theirouter diameters are reduced in comparison to their inflated outerdiameters. Middle portion 240 is longitudinally contracted (as comparedto the longitudinally extended configuration of FIG. 2). In thisconfiguration, electroporation device 200 is configured to beendoscopically deployed within the GI tract of a patient using endoscope300.

In some embodiments, electroporation device 200 is configured to bedeployed via a working channel of an endoscope or laparoscope. In someembodiments, electroporation device 200 is configured to be deployedover a guidewire instead of over endoscope 300. One or more radiopaquemarkers or echogenic markers, or both, may be disposed on one or morelocations or on one or more portions of electroporation device 200(e.g., on the balloons 220 and/or 230).

Referring to FIG. 4, electroporation device 200 can be deployed withinduodenum 120 to provide electroporation treatments to a patient.Electroporation device 200 can treat obesity and diabetes usingelectroporation to modulate the duodenal mucosa 122.

Electroporation device 200 is shown after removal of a delivery device,such as endoscope 300 (FIG. 3). In some deployment techniques, endoscope300 is used to position the distal balloon 230 in a desired locationwithin duodenum 120 or distal small intestines (such as the jejunum). Insome deployment techniques, electroporation device 200 is positionedwithin a working channel of an endoscope. Then, distal balloon 230 isinflated to temporarily fix distal balloon 230 in the desired location.Next, endoscope 300 is pulled back, proximally. In doing so, middleportion 240 is longitudinally extended and laterally deflected withinduodenum 120. When proximal balloon 220 is positioned in a desiredlocation within duodenum 120, then proximal balloon 220 is inflated totemporarily fix proximal balloon 220 in the desired location. Then,endoscope 300 can be further pulled back proximally (and may becompletely disengaged from electroporation device 200.

When fully deployed, proximal balloon 220 is inflated to occlude theproximal portion of the duodenum 120, and distal balloon 230 is inflatedto occlude the distal portion of duodenum 120. The interior space ofduodenum 120 defined between the proximal balloon 220 and the distalballoon 230 is substantially sealed from other portions of the GI tract100.

With the balloons 220, 230 inflated, an electrically conductive liquid400 can be delivered into the interior space between the balloons 220,230 by injecting it via lumen 212 and apertures 246 (refer to FIG. 2).In some implementations, saline is used for electrically conductiveliquid 400. In some implementations, hypertonic saline is used forelectrically conductive liquid 400. In some implementations, dextrose isused for electrically conductive liquid 400. Other types of electricallyconductive liquid 400 can also be used. For example, conductive liquid400 can include, but is not limited to, cation-rich solutions such assodium ion, potassium ion, calcium ion, magnesium ion, etc., of varyingconcentrations, for example 3% sodium chloride, calcium chloride,calcium carbonate, potassium chloride, potassium carbonate, etc. In thesame regard, ionized forms of known medicinal solutions or drugs may beinfused into the interior space between the balloons 220, 230 to beplaced intracellularly in target cells, such as the duodenal mucosa,both for stimulation, regeneration, and otherwise targeted therapies forobesity and diabetes. The electroporation and/or current source willserve as a vehicle for intracellular delivery and the electronictransfer of the electroporation energy is achieved by ionization ofthese solutions. In some implementations, a combination of differenttypes of drugs and or other types of electrically conductive liquid 400are used.

Electrodes 244 can be energized to provide a source of electroporationenergy. The electrically conductive liquid 400 within the interior spacebetween the balloons 220, 230 will carry the electrical energy from theelectrodes 244 to duodenal mucosa 122. The pressure of electricallyconductive liquid 400 within the interior space should be adjusted to behigh enough such that electrically conductive liquid 400 is forced intothe crypts of duodenal mucosa 122.

In some implementations, a sequential ablation technique where salineand dextrose are circulated in the interior space between the balloons220, 230 sequentially, while delivering electroporation energythroughout is used. This would be a mechanical method to create phasedablation to minimize sloughing and essentially completely preventbleeding or stricture. There would be a timed sequence with a pre-timeset of two pumps that would create the phased delivery. The setup wouldbe one pump continuously infuses the saline, and through the tubing asecond pump will change the volume of dextrose or lactated ringers goingin. The electroporation source could be kept constant, or alternativelymore than one electrode placed along electroporation device 200 and amore standard electronic phasing circuit can be implemented.

In some embodiments, a hydrogel is used to electrically carryelectroporation energy. In some cases the hydrogel may facilitate longerlasting contract of electroporation energy with duodenal mucosa 122,including within the crypts of duodenal mucosa 122.

In some embodiments, proximal balloon 220 is positioned so as to envelopthe ampulla and to protect the ampulla during electroporation.Accordingly, in some embodiments proximal balloon 220 is highlycompliant to provide such protection to the ampulla.

After administration of electroporation using electroporation device 200and electrically conductive liquid 400, the delivery of theelectroporation energy can be stopped. Then the balloons 220, 230 can bedeflated, and electroporation device 200 can be removed from GI tract100 of the patient.

Referring to FIG. 5, another example electroporation device 500embodiment is illustrated. Electroporation device 500 includes a balloon510, a shaft 520, and one or more electrodes 530. Balloon 510 iscircumferentially disposed about shaft 520. Electrodes 530 are disposedon the outer surface of balloon 520.

Shaft 520 defines a lumen 522 that is analogous to lumen 212 ofelectroporation device 200. In some embodiments, shaft 520 also definesone or more apertures 526. Apertures 526 allow an electricallyconductive liquid to flow from lumen 522 to an interior space of balloon510. However, such electrically conductive liquid is optional. That is,in some embodiments electrodes 530 deliver electroporation energy toduodenal mucosa 122 without the use of electrically conductive liquid.

Balloon 510 can be made of the materials described above in reference toballoons 220, 230 of electroporation device 200, for example. In someembodiments, the longitudinal length of balloon 510 is about 15 cm. Thelongitudinal length of balloon 510 is scalable to any suitable size. Forexample, in some embodiments the longitudinal length of balloon 510 isin a range from about 10 cm to about 20 cm, or from about 15 cm to about25 cm, or from about 10 cm to about 25 cm, or from about 15 cm to about20 mm, or from about 10 cm to about 15 cm. Balloon 510 can have aninflated maximum outer diameter that is sized as described above inreference to balloons 220, 230 of electroporation device 200, forexample.

In some embodiments, electroporation device 500 is an example of aweeping balloon design. That is, balloon 510 can be partly or fully madefrom a porous or microporous material such that an electricallyconductive liquid can elute, weep, or be otherwise transmitted throughballoon 510 to form droplets 540. Accordingly, droplets 540 ofelectrically conductive liquid can carry electroporation energy fromelectrodes 530 to duodenal mucosa 122. In some embodiments, a hydrogelis used to electrically carry electroporation energy. In some cases thehydrogel may facilitate longer lasting contract of electroporationenergy with duodenal mucosa 122, including within the crypts of duodenalmucosa 122.

Electrodes 530 can be analogous to electrodes 244 of electroporationdevice 200 as described above.

Referring to FIG. 6, another example electroporation device 600embodiment is illustrated. Electroporation device 600 is an example of aweeping balloon design. That is, electroporation device 600 includes aballoon 610 that can be partly or fully made from a porous ormicroporous material such that an electrically conductive liquid or gelcan elute, weep, or be otherwise transmitted through balloon 610 to formdroplets 640. Electroporation device 600 is shown with balloon 610 inlongitudinal cross-section to provide visibility within the interiorspace defined by balloon 610.

Electroporation device 600 includes balloon 610, a shaft 620, and one ormore electrodes 630. Balloon 610 is circumferentially disposed aboutshaft 620. Electrodes 630 are disposed on the outer surface of shaft620. Electrodes 630 can be analogous to electrodes 244 ofelectroporation device 200 as described above.

The size and materials of construction of balloon 610 can be analogousto those of balloon 510 described above.

Shaft 620 defines a lumen 622 that is analogous to lumen 212 ofelectroporation device 200. Shaft 620 also defines one or more apertures626. Apertures 626 allow an electrically conductive liquid to flow fromlumen 622 to an interior space of balloon 610 where electricallyconductive liquid can be energized with electroporation energy fromelectrodes 630. Thereafter, the energized electrically conductive liquidcan elute, weep, or be otherwise transmitted through balloon 610 to formdroplets 640 that carrying electroporation energy to duodenal mucosa122, including within the crypts of duodenal mucosa 122.

Referring also to FIG. 7, electroporation device 600 can be deployedwithin duodenum 120 or more distally in the small intestines such as inthe jejunum to provide electroporation treatments to a patient.Electroporation device 600 can treat obesity and diabetes usingelectroporation to modulate the duodenal or distal small intestinalmucosa 122. Electroporation device 500 (FIG. 5) can be implemented in ananalogous manner.

Electroporation device 600 is shown after removal of a delivery device,such as endoscope 300 (FIG. 3) or a guiding wire. In some deploymenttechniques, endoscope 300 is used to position the balloon 620 in adesired location within duodenum 120. Then balloon 620 is inflated totemporarily fix balloon 620 in the desired location. Then, endoscope 300can be further pulled back proximally (and may be completely disengagedfrom electroporation device 600.

With balloon 620 inflated, an electrically conductive liquid can beinfused into the interior space of balloon 620 by injecting it via lumen622 and apertures 626 (refer to FIG. 6). In some implementations, salineis used for electrically conductive liquid. In some implementations,hypertonic saline is used for electrically conductive liquid. In someimplementations, dextrose is used for electrically conductive liquid.Other types of electrically conductive liquid can also be used. In someimplementations, a combination of different types of electricallyconductive liquid are used.

Electrodes 630 can be energized to provide a source of electroporationenergy. The electrically conductive liquid within the interior space ofballoon 610 will carry the electrical energy from the electrodes 630,through the wall of balloon 610, and to duodenal mucosa 122, includinginto the crypts of duodenal mucosa 122.

In some embodiments, a hydrogel is used to electrically carryelectroporation energy. In some cases the hydrogel may facilitate longerlasting contract of electroporation energy with duodenal mucosa 122,including within the crypts of duodenal mucosa 122.

After administration of electroporation using electroporation device 600and the electrically conductive liquid, the delivery of theelectroporation energy can be stopped. Then balloon 620 can be deflated,and electroporation device 600 can be removed from GI tract 100 of thepatient.

Referring to FIGS. 8 and 9, another example electroporation device 700embodiment is illustrated. Electroporation device 700 can be used totreat conditions such as obesity and diabetes using electroporation tomodulate, for example, the duodenal mucosa 122.

In the depicted embodiment, electroporation device 700 includes anendoscope 710, a proximal balloon 720, a distal balloon 730, and acatheter 740 that includes one or more electrodes 742. Proximal balloon720 is located at a distal end region of endoscope 710. Catheter 740 isconfigured to be slidably disposed within a working channel of endoscope710. Distal balloon 730 is attached at a distal end region of catheter740. Electrodes 742 are attached at spaced-apart locations along thelength of catheter 740.

In some embodiments, proximal balloon 720 is attached to the distal endregion of endoscope 710 (and endoscope 710 includes an inflation lumen).In some embodiments, proximal balloon 720 is attached to a distalportion of a sheath (not shown) that includes an inflation lumen, andthat defines a larger lumen that can slidably receive endoscope 710.

Balloons 720 and 730 can be compliant balloons that are sized andconstructed like balloons 220, 230 of electroporation device 200, forexample. Electrodes 742 can be analogous to electrodes 244 ofelectroporation device 200 as described above.

Endoscope 710 includes a lumen (e.g., an irrigation lumen) through whichelectrically conductive liquid 400 can flow. When electroporation device700 is in use (as depicted in FIG. 9), electrically conductive liquid400 can flow through the lumen of endoscope 710, and thereafter residein duodenum 120 between proximal balloon 720 and distal balloon 730. Inthis arrangement, energy from energized electrodes 742 can be conductedby electrically conductive liquid 400 to duodenal mucosa 122, includingwithin the crypts of duodenal mucosa 122.

Referring to FIGS. 10 and 11, another example electroporation device 800embodiment is illustrated. Electroporation device 800 can be used totreat conditions such as obesity and diabetes using electroporation tomodulate, for example, the duodenal mucosa 122. In some embodiments,electroporation device 800 is configured to be slidably disposed withina working channel of an endoscope such that electroporation device 800can be delivered via the endoscope. In some embodiments, electroporationdevice 800 includes a lumen that can slidably receive a guidewire suchthat electroporation device 800 can be delivered over a wire.

In the depicted embodiment, electroporation device 800 includes cathetershaft 810, a proximal balloon 820, a distal balloon 830, one or moreelectrodes 812, and one or more apertures 814. Proximal balloon 820 isattached to catheter shaft 810 at any suitable distance proximal fromthe distal end of catheter shaft 810. Distal balloon 830 is attached ata distal end region of catheter shaft 810. Electrodes 842 are attachedat spaced-apart locations along the length of catheter shaft 810.Apertures 814 are defined at spaced-apart locations along the length ofcatheter shaft 810.

Balloons 820 and 830 can be compliant balloons that are sized andconstructed like balloons 220, 230 of electroporation device 200, forexample. Electrodes 812 can be analogous to electrodes 244 ofelectroporation device 200 as described above.

Catheter shaft 810 defines one or more apertures 814 through whichelectrically conductive liquid 400 can flow. When electroporation device800 is in use (as depicted in FIG. 11), electrically conductive liquid400 can flow through a lumen of catheter shaft 810, exit catheter shaft810 via apertures 814, and thereafter reside in duodenum 120 betweenproximal balloon 820 and distal balloon 830. In this arrangement, energyfrom energized electrodes 812 can be conducted by electricallyconductive liquid 400 to duodenal mucosa 122, including within thecrypts of duodenal mucosa 122.

Referring to FIGS. 12 and 13, another example electroporation device 900embodiment is illustrated. Electroporation device 900 can be used totreat conditions such as obesity and diabetes using electroporation tomodulate, for example, the duodenal mucosa 122.

In the depicted embodiment, electroporation device 900 includes anendoscope overtube 910, a proximal balloon 920, a distal balloon 930, aradially and/or longitudinally expandable middle portion 940, and anelectroporation catheter 950 that includes one or more electrodes 952.An endoscope 300, along with the electroporation device 900, comprisesan electroporation device system.

Proximal balloon 920 is attached to overtube 910 in a circumferentialfashion. Middle portion 940 extends between proximal balloon 920 anddistal balloon 930. Each of the overtube 910, proximal balloon 920,distal balloon 930, and middle portion 940 define a lumen that canslidably receive endoscope 300.

Within the lumen of distal balloon 930 is a distal valve 932. Valve 932allows the passage of an instrument (e.g., endoscope 300 or guidewire)therethrough. But, when no such instrument is in contact with valve 932,valve 932 acts as a fluidic closure at the distal end of the lumen sothat the lumen is dead ended at or near distal balloon 930.

Electroporation catheter 950 is configured to be slidably disposedwithin a working channel of endoscope 300 (as depicted in FIG. 13 whereendoscope 300 has been pulled back such that its distal tip is withinproximal balloon 920). Electrodes 952 are attached at spaced-apartlocations along the length of electroporation catheter 950.

Balloons 920 and 930 can be compliant balloons that are sized andconstructed like balloons 220, 230 of electroporation device 200, forexample. Electrodes 952 can be analogous to electrodes 244 ofelectroporation device 200 as described above.

Middle portion 940 is made of a foldable mesh or porous material. Hence,middle portion 940 can be radially and/or longitudinally compressed (asshown in FIG. 12) for delivery of the electroporation device 900 intothe GI tract. Additionally, middle portion 940 can be radially and/orlongitudinally extended (as shown in FIG. 13) while electroporationdevice 900 is administering electroporation to modulate duodenal mucosa122.

Endoscope 300 includes a lumen (e.g., an irrigation lumen) through whicha supply of electrically conductive liquid 400 can be delivered asdepicted in FIG. 13.

Using electroporation device 900 and endoscope 300 to deliverelectroporation as depicted in FIG. 13, the depths and cell compositionof the crypts and villi of duodenal mucosa 122 can be modulated. Usingsuch devices and techniques, weight loss and/or control of diabetes byreducing the caloric absorption, by increasing gut hormones, and/or byre-setting the diseased intestinal mucosa of an individual can beachieved.

When electroporation device 900 is in use, electrically conductiveliquid 400 can flow through the lumen of endoscope 300, pass through theporous material of middle portion 940, and thereafter reside in duodenum120 between proximal balloon 920 and distal balloon 930. In thisarrangement, energy from energized electrodes 952 can be conducted byelectrically conductive liquid 400 to duodenal mucosa 122, includingwithin the crypts of duodenal mucosa 122. In some cases, the irregularwall topography and/or crypts of duodenal mucosa 122 may become moreplanar by the mechanical forces applied by electroporation device 900 toduodenal mucosa 122.

ADDITIONAL EMBODIMENTS AND/OR ADDITIONAL FEATURES

In some embodiments, the electroporation devices and systems providedherein can include design features to prevent or inhibit undesiredelectro-stimulation of non-targeted bodily structures such as, but notlimited to, the patient's heart and/or nervous system. For example, insome embodiments insulating elements can be included on or adjacent toone or more portions of the electroporation devices provided herein.Such insulating elements can block the emitted energy from followingparticular paths so as to protect non-targeted bodily structures. Insome embodiments, insulated bipolar electroporation is incorporated(e.g., where the electrodes are mounted within or on a balloon, and/orseparate electrodes are placed in the proximal duodenum). Suchelectrodes can be used as the anode or cathode when the complimentarycathode or anode are located within, on, or as a separate electrode to aballoon placed in the distal duodenum. For example, the insulation canbe an insulating coating on a particular side of a balloon, a secondballoon which insulated, or an air sac acting as insulation element tocover one side of the external surface of a balloon. In someembodiments, such insulating techniques can be used to cover one side ofthe external surface of a weeping balloon. In some embodiments, theenergy delivery devices make use of the curvature of the duodenum toprovide the desired electroporation without extra duodenum stimulation.In some embodiments, bipolar electrodes are included (e.g., a distalelectrode and a proximal electrode on an electroporation device).

In some cases when the aforementioned insulation is included, because ofthe insulation on the external surface, the adjacent duodenal tissue tothe insulated surface will require remaining treatment. To do this, forthe proximal duodenum some embodiments use a return electrode in thegreater curvature of the stomach, and for the distal and mid duodenumelectrodes are placed in the proximal jejunum or other portions of theGI tract. These embodiments can be in alternatives or additions to thealready described configuration with the return electrode placed on theabdomen, on the back, or somewhere else externally.

In some embodiments, undesired electro-stimulation of non-targetedbodily structures can be avoided or inhibited using a unique method ofelectroporation where pulse DC currents are delivered judicially atvarious times throughout the cardiac cycle. In some embodiments,continuous electroporation throughout the cardiac cycle is given;however, if ectopy or any change in the cardiac rhythm is noted, thenthat trigger (e.g., the far-field ventricular electrogram) can be usedas the sensor wherein the energy delivery will be limited to only thefirst 200 msec, for example, following the detected far-field QRS. Insome embodiments, an internal ECG sensor and electric field sensor canbe placed on the insulated surface of the electroporation device. Ifthere is no electric field pointing in the direction of heart, thensubstantially no danger of electroporation interfering with normal heartrhythm exists, and continuous electroporation can be carried out. Ifthere is electric field pointing towards the direction of the heart,then the signal from the internal ECG sensor can be used for timing theelectroporation pulse delivery so that the pulse is not delivered in themost vulnerable phase of heart rhythm.

While the implementations described above pertain to the delivery ofelectroporation to the duodenal cells relevant for the management ofdiabetes and obesity, the duodenum and the adjacent portions of the GItract also offer unique vantage points to deliver electroporation andother energy delivery to neighboring structures. Such neighboringstructures included, but are not limited to, the celiac ganglion andplexus, lymphatic ganglia and plexus, and the renal nerves andassociated plexuses. Since the GI tract is curved and tortuous, bipolarelectroporation can be carried out by deploying a distal electrode and aproximal electrodes along GI tract in such a way that the electric fieldcreated in between these two points will cover the visceral tissues andorgans on the path outside of GI tract. Therefore, therapy can bedelivered using some embodiments provided herein for the treatment ofconditions such as, but not limited to, pancreatic malignancy,pancreatic and deep visceral pain and for hypertension by reversible andirreversible electroporation of the ganglia. Such hypertensionmanagement, in turn, would help with a metabolic syndrome that resultsfrom the combination of obesity, diabetes, and hypertension.

In some additional embodiments, stent devices for treating healthconditions including obesity and diabetes are combination devices thatcombine the benefit of placing internal conduits covering the surface ofthe duodenal mucosa along with the benefits of more permanentelectroporation-based modulation. By combining the two (a stent andelectroporation electrodes), a system to secure the stent is attained.The conduit is essentially a covered stent, but instead of a crossingdiamond-type of scaffold, linear struts are included. The purpose of thelinear struts is to elute a gel which on electroporation will adhere tothe mucosa, providing a secure hold. Between the linear struts, there isnothing apposing the covered stent to the duodenal mucosa so thatsecretions may still come out and enter the duodenal lumen. Food wouldpass through the stent, and thus a two-pronged approach for treatingthis region can be attained. Additional iterations could include one-wayvalves placed in between the linear struts, or a blood sugar sensor/RFfeedback for electroporation release to titrate for an individual anideal total energy load to maintain blood sugars.

In another embodiment using a stent conduit, the known benefits of arouxen-Y procedure with that of electroporation are combined. Here, adeflectable catheter which has both an internal lumen for a wire, RFelectrodes which can place energy on the central wire, and a secondmonorail wire is maneuvered out of the lumen of the proximal duodenum.The catheter is then moved to enter the proximal jejunum, and then isdeflected back towards its initial entry site, and through the monoraillumen, a snare is used to grab the central lumen wire. Thus, a rail thatessentially leaves the lumen and reenters, feeding back to itself iscreated. Over this wire, at least three iterations are possible: a) acovered stent/conduit is advanced over the distal wire, and then tosecure it, a suture is advanced over both proximal and distal wires andtightened on the duodenum, b) the conduit is placed over the proximalwire following its course and essentially creating the anastomosisexternally and with a similar locking mechanism to keep it in place, andc) there is a combination of the prior two such that a conduit, acovered stent, and a locking mechanism are all used in a given patient.

In some embodiments, the stent could be adjusted with noninvasivemethods, including magnets or endoscopically placed stents, and thestent itself may be delivered via a laparoscopic approach.

Additionally, the devices and techniques described herein can be appliedin contexts beyond that of the duodenum. For example, the devices andtechniques described herein can be applied in the contexts of the mucosaof the distal small and large intestines, and other endoluminal organssuch as the gallbladder, pancreas, and in the arteriovenous system.

Additionally, the devices and techniques describes herein can be appliedto pherese drugs to cells within the mucosa of the duodenum 122 to altertheir function. For example drugs such as rapamycin know to modulate theeffects of paneth and stem cells within the crypts of the smallintestines can be ionized and pheresed into these cell usingelectroporation. Furthermore, sweet substances known to stimulate theenteroendocrine cells within the villi of the duodenum can be applied.Similarly, tacrolimus can be used to stimulate stem cells in some cases.As such, these devices and techniques may cycle energy alone, drug orsubstance alone, or in combination to treat obesity and diabetes.

Some of the devices and methods provided herein can also incorporatestimulatory electrodes or other devices that can be used to ascertaincell death or activity, or to measure the temperature, electrical fieldstrength, and/or charge density of the delivered electroporativetherapy.

Some of the devices provided herein which incorporate a balloon orballoon-like elements may be used to achieve stretch of the intestine,not only to increase the surface area of contact to the crypt cells, butby virtue of the stretch itself produce membrane poration and inducedapoptosis.

Some embodiments of the balloon or mesh incorporated devices aredesigned to increase the charge density of delivery throughinjection-like ports that may be achieved by a serrated surface oractual expandable, low surface area, pointed elements. These may serveas actual injection ports for charge or an electrolyte-rich solution totransfer the electroporation rendering energy or serve as regions ofhigh electron or other electrical force density by virtue of theirshape, which would match the required area where the increased densityof charge is required and thus minimizing risks of electrical or thermalinjury to the non-targeted sites.

It should be understood that one or more of the features describedanywhere herein may be combined with one or more other featuresdescribed anywhere herein to create hybrid devices and/or methods,without departing from the scope of this disclosure.

While this specification contains many specific implementation details,these should not be construed as limitations on the scope of anyinvention or of what may be claimed, but rather as descriptions offeatures that may be specific to particular embodiments of particularinventions. Certain features that are described in this specification inthe context of separate embodiments can also be implemented incombination in a single embodiment. Conversely, various features thatare described in the context of a single embodiment can also beimplemented in multiple embodiments separately or in any suitablesubcombination. Moreover, although features may be described herein asacting in certain combinations and even initially claimed as such, oneor more features from a claimed combination can in some cases be excisedfrom the combination, and the claimed combination may be directed to asubcombination or variation of a subcombination.

Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. In certain circumstances, multitasking and parallel processingmay be advantageous. Moreover, the separation of various system modulesand components in the embodiments described herein should not beunderstood as requiring such separation in all embodiments, and itshould be understood that the described program components and systemscan generally be integrated together in a single product or packagedinto multiple products.

Particular embodiments of the subject matter have been described. Otherembodiments are within the scope of the following claims. For example,the actions recited in the claims can be performed in a different orderand still achieve desirable results. As one example, the processesdepicted in the accompanying figures do not necessarily require theparticular order shown, or sequential order, to achieve desirableresults. In certain implementations, multitasking and parallelprocessing may be advantageous.

1.-29. (canceled)
 30. A method of treating diabetes in a patient,comprising: advancing an electroporation device comprising one or moreelectrodes into a duodenum of the patient; and deliveringelectroporation energy to the duodenum using the one or more electrodesto treat diabetes.
 31. The method of claim 30 further comprisingtransitioning the electroporation device from a first configuration to asecond configuration.
 32. The method of claim 31, wherein the firstconfiguration is a contracted configuration and the second configurationis an expanded configuration.
 33. The method of claim 31, whereintransitioning the electroporation device to the second configurationstretches at least a portion of the duodenum.
 34. The method of claim30, wherein the electroporation energy is delivered to crypts of aduodenal mucosa of the duodenum.
 35. The method of claim 30, wherein theelectroporation energy comprises pulse currents.
 36. The method of claim30, wherein the one or more electrodes comprise bipolar electrodes. 37.The method of claim 30, wherein the one or more electrodes comprise aplurality of spaced-apart electrodes.
 38. The method of claim 30,wherein the electroporation device comprises a rolled-up membercomprising the one or more electrodes.
 39. The method of claim 38,wherein the one or more electrodes are disposed on an outer surface ofthe rolled-up member.
 40. The method of claim 38, wherein the rolled-upmember defines one or more apertures.
 41. The method of claim 38 furthercomprising delivering a fluid into an interior space of the duodenumthrough the one or more apertures.
 42. The method of claim 41, whereinthe fluid is circulated in the interior space of the duodenum whiledelivering the electroporation energy.
 43. The method of claim 41,wherein at least a portion of the rolled-up member is spaced apart froman inner wall of the duodenum, and wherein the fluid conducts at leastsome of the electroporation energy to the inner wall of the duodenum.44. The method of claim 41, wherein the fluid comprises a hydrogel. 45.The method of claim 41, wherein the fluid comprises an electricallyconductive liquid.
 46. The method of claim 41, wherein the fluidcomprises a drug.
 47. The method of claim 46, wherein delivering thefluid comprises pheresing the drug to cells within a duodenal mucosa ofthe duodenum.
 48. The method of claim 38, wherein the rolled-up memberdefines a lumen and the method further comprises advancing an endoscopethrough the lumen of the rolled-up member.
 49. The method of claim 30further comprising measuring one or more characteristics of thedelivered electroporation energy using the one or more electrodes.